In HIV/AIDS studies, viral load (the number of copies of HIV-1 RNA) and CD4 cell counts are important biomarkers of the severity of viral infection, disease progression, and treatment evaluation. Recently, joint models, which have the capability on the bias reduction and estimates' efficiency improvement, have been developed to assess the longitudinal process, survival process, and the relationship between them simultaneously. However, the majority of the joint models are based on mean regression, which concentrates only on the mean effect of outcome variable conditional on certain covariates. In fact, in HIV/AIDS research, the mean effect may not always be of interest. Additionally, if obvious outliers or heavy tails exist, mean regression model may lead to non-robust results. Moreover, due to some data features, like left-censoring caused by the limit of detection (LOD), covariates with measurement errors and skewness, analysis of such complicated longitudinal and survival data still poses many challenges. Ignoring these data features may result in biased inference.
Compared to the mean regression model, quantile regression (QR) model belongs to a robust model family, which can give a full scan of covariate effect at different quantiles of the response, and may be more robust to extreme values. Also, QR is more flexible, since the distribution of the outcome does not need to be strictly specified as certain parametric assumptions. These advantages make QR be receiving increasing attention in diverse areas. To the best of our knowledge, few study focuses on the QR-based joint models and applies to longitudinal-survival data with multiple features.
Thus, in this dissertation research, we firstly developed three QR-based joint models via Bayesian inferential approach, including: (i) QR-based nonlinear mixed-effects joint models for longitudinal-survival data with multiple features; (ii) QR-based partially linear mixed-effects joint models for longitudinal data with multiple features; (iii) QR-based partially linear mixed-effects joint models for longitudinal-survival data with multiple features. The proposed joint models are applied to analyze the Multicenter AIDS Cohort Study (MACS) data. Simulation studies are also implemented to assess the performance of the proposed methods under different scenarios. Although this is a biostatistical methodology study, some interesting clinical findings are also discovered.
| Identifer | oai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-8653 |
| Date | 17 November 2017 |
| Creators | Zhang, Hanze |
| Publisher | Scholar Commons |
| Source Sets | University of South Flordia |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Graduate Theses and Dissertations |
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